In recent years, successive clonings of glutamate receptor genes have revealed that glutamate receptors have a surprisingly large number of subtypes. At present, glutamate receptors are classified into two major groups: an “ionotropic type in which the receptor has a ion channel type structure” and a “metabotropic type in which the receptor is coupled with G-protein” (see Science, 258, p. 597-603, 1992 (Non-Patent Document 1 mentioned below)). The ionotropic glutamate receptors are classified pharmacologically into three sub-groups: N-methyl-D-asparaginic acid (NMDA); α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA); and kainate (see Non-Patent Document 1). The metabotropic glutamate receptors are classified into eight sub-groups from type 1 to type 8 (see J. Neurosci., 13, p. 1372-1378, 1993 (Non-Patent Document 2 mentioned below), and Neuropharmacol., 34, p. 1-26, 1995 (Non-Patent Document 3 mentioned below)).
The metabotropic glutamate receptors are classified pharmacologically into three groups. Of these, the Group II receptors (mGluR2/mGluR3) bind with adenylcyclase, and inhibit the Forskolin stimulated accumulation of cyclic adenosine monophosphate (cAMP) (see Trends Pharmacol. Sci., 14, 13, 1993 (Non-Patent Document 4 mentioned below)). Thus, it is suggested that compounds, which antagonize the action of Group II metabotropic glutamate receptors, will be effective for the treatment and prevention of acute and chronic psychiatric disorders and neurological diseases.
LIST OF RELATED DOCUMENTSNon-Patent Document 1:Science, 258, p. 597-603, 1992Non-Patent Document 2:J. Neurosci., 13, p. 1372-1378, 1993Non-Patent Document 3:Neuropharmacol., 34, p. 1-26, 1995Non-Patent Document 4:Trends Pharmacol. Sci., 14, p. 13, 1993
The object of the present invention is to provide a drug that antagonizes the action of Group II metabotropic glutamate receptors, and would be effective for the treatment and prevention of psychiatric disorders such as schizophrenia, anxiety and related ailments thereof, depression, bipolar disorder and epilepsy, and also effective for the treatment and prevention of neurological diseases such as drug dependence, cognitive disorder, Alzheimer's disease, Huntington's chorea, Parkinson's disease, dyskinesia associated with muscular rigidity, cerebral ischaemia, cerebral failure, myelopathy and head trauma.